Further investigation of the rapid-onset and short-duration action of the G protein-biased µ-ligand oliceridine.
Biochem Biophys Res Commun
; 534: 988-994, 2021 01 01.
Article
em En
| MEDLINE
| ID: mdl-33139013
ABSTRACT
TRV130 (oliceridine), a G protein-biased ligand for µ-opioid receptor, has recently been synthesized. It is considered to have strong antinociceptive effects and only minor adverse effects. However, whether or not oliceridine actually exhibits an ideal pharmacological profile as an analgesic has not yet been fully clarified in animal studies. This study examined the pharmacological profile of oliceridine in cells and animals. Oliceridine (10 µM) did not produce any µ-opioid receptor internalization in cells even though it increased impedance, which reflects the activation of Gi protein using the CellKey™ system, and inhibited the formation of cAMP. In mice, oliceridine (0.3-10 mg/kg) produced a dose-dependent antinociceptive effect with a rapid-onset and short-duration action in the hot-plate test, as well as antihyperalgesia after sciatic nerve ligation without the development of antinociceptive tolerance using the thermal hyperalgesia test. On the other hand, oliceridine inhibited gastrointestinal transit. Furthermore, oliceridine produced rapid-onset hyperlocomotion at antinociceptive doses; sensitization developed in mice and an emetic effect was observed in ferrets. These results indicate that, although oliceridine may produce dopamine-related behaviors even through selective stimulation of the G-protein-biased µ-opioid receptor pathway, it still offers advantages for breakthrough pain without antinociceptive tolerance with adequate doses.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Compostos de Espiro
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Tiofenos
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Receptores Opioides mu
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Proteínas de Ligação ao GTP
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Analgésicos
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Neuralgia
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão